Seattle Genetics to Present Clinical Data from Broad ADCETRIS® (Brentuximab Vedotin) Development Program and Novel Antibody-Drug Conjugate (ADC) SGN-CD19A at ASH 2013

Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that multiple abstracts will be presented at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in New Orleans, Louisiana, December 7-10, 2013, highlighting the following:

• Clinical data for ADCETRIS (brentuximab vedotin) in CD30-positive lymphomas, including Hodgkin lymphoma (HL), mature T-cell lymphoma (MTCL), cutaneous T-cell lymphoma (CTCL) and diffuse B-cell lymphoma (DLBCL);
• Interim phase 1 clinical data for SGN-CD19A, a novel antibody-drug conjugate (ADC), in acute lymphoblastic leukemia (ALL); and
• Final phase 1 data from two ADC candidates that utilize Seattle Genetics’ proprietary technology being developed by Genentech, a member of the Roche Group (SIC: RO, ROG; OTCQX: RHHBY), including an anti-CD22 ADC (pinatuzumab vedotin, RG7593) and an anti-CD79b ADC (polatuzumab vedotin, RG7596).

“The presentations at ASH demonstrate the breadth of our development program for ADCETRIS in CD30-positive malignancies, including frontline and relapsed patients and disease areas ranging from Hodgkin lymphoma to mature T-cell lymphoma and diffuse large B-cell lymphoma,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Beyond ADCETRIS, we continue to make progress in advancing our robust ADC pipeline, including SGN-CD19A, which is currently being evaluated in ALL and aggressive non-Hodgkin lymphoma. Finally, our collaborators continue to advance potential therapeutic options for patients and are making progress with ADCs utilizing our technology.”

ADCETRIS is an ADC directed to CD30, which is known to be expressed in HL and systemic anaplastic large cell lymphoma (sALCL), as well as in many types of CTCL, B-cell lymphomas and MTCL. Across corporate and investigator-sponsored trials, ADCETRIS is being evaluated in more than 20 ongoing clinical trials, including four phase 3 studies. ADCETRIS is currently not approved for use in CTCL, B-cell non-Hodgkin lymphoma, salvage HL or frontline treatment of MTCL and HL.

SGN-CD19A is an ADC targeting CD19, a protein expressed broadly on B-cell malignancies. Preclinical data presented at the 2011 American Association for Cancer Research Annual Meeting demonstrated that SGN-CD19A effectively binds to target cells, internalizes and induces potent cell-killing activity and durable tumor regressions at low doses in multiple cancer models. SGN-CD19A is being evaluated in two ongoing phase 1 clinical trials for patients with B-cell ALL and aggressive non-Hodgkin lymphoma (NHL).

With over a decade of experience and knowledge in ADC innovation, Seattle Genetics is the leader in developing ADCs, a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. Of the approximately 30 ADC candidates in development, more than half utilize Seattle Genetics’ proprietary ADC technology. ADCETRIS is the first drug approved utilizing this technology.

Multiple corporate, investigator and collaborator presentations will be featured at ASH. Abstracts can be found at www.hematology.org and include the following:

Saturday, December 7, 2013

• A First-in-Human Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Acute Leukemia and Highly Aggressive Lymphoma (Abstract #1437, poster presentation)
• Three-Year Survival Results from an Ongoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (Abstract #1809, poster presentation)
• FDG-PET Adapted Sequential Therapy With Brentuximab Vedotin and Augmented ICE Followed By Autologous Stem Cell Transplant For Relapsed and Refractory Hodgkin Lymphoma (Abstract #2099, poster presentation)

Monday, December 9, 2013

• Brentuximab Vedotin Administered Before, During, and After Multi-agent Chemotherapy in Patients with Newly-diagnosed CD30+ Mature T- and NK-cell Lymphomas (Abstract #4386, poster presentation)
• A Phase 2 Study of Single-Agent Brentuximab Vedotin for Front-Line Therapy of Hodgkin Lymphoma in Patients Age 60 Years and Above: Interim Results (Abstract #4389, poster presentation)
• Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Abstract #367, oral presentation at 10:30 a.m. ET)
• Three-year Follow-up Data and Characterization of Long-Term Remissions from an Ongoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #4382, poster presentation)
• Phase 1/2 Study Of Brentuximab Vedotin In Pediatric Patients With Relapsed Or Refractory (R/R) Hodgkin Lymphoma (HL) Or Systemic Anaplastic Large-Cell Lymphoma (sALCL): Preliminary Phase 2 Data For Brentuximab Vedotin 1.8 Mg/Kg In The HL Study Arm (Abstract #4378, poster presentation)
• Fucosylation Inhibitor, 2-fluorofucose, Inhibits NF-ĸB Activation and Vaso-occlusion in Transgenic Sickle Mice (Abstract #730, oral presentation at 7:00 p.m. ET)
• Final Results of a Phase I Study of the Anti-CD22 Antibody-Drug Conjugate DCDT2980S with or without Rituximab in Patients with Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma (Abstract #4399, poster presentation)
• Final Results of a Phase I Study of the Anti-CD79b Antibody-Drug Conjugate DCDS4501A in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (Abstract #4400, poster presentation)

Tuesday, December 10, 2013

• A Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-positive Non-Hodgkin Lymphomas: Interim Results in Patients with DLBCL and Other B-cell Lymphomas (Abstract #848, oral presentation at 7:45 a.m. ET)

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS received accelerated approval from the U.S. Food and Drug Administration (FDA) and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS also received marketing authorization by regulatory authorities in Switzerland and South Korea. See important safety information below.

Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.

About SGN-CD19A

SGN-CD19A is an ADC comprised of an anti-CD19 monoclonal antibody linked to a synthetic cytotoxic cell-killing agent, monomethyl auristatin F (MMAF), using Seattle Genetics’ industry leading proprietary technology. The ADC is designed to be stable in the bloodstream, and to release its cytotoxic agent upon internalization into CD19-expressing tumor cells. CD19 is expressed in ALL and some types of NHL, including DLBCL. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity.

About Seattle Genetics

Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin) is an ADC that, in collaboration with Millennium: the Takeda Oncology Company, has been approved for two indications in more than 35 countries, including the U.S., European Union and Canada. Additionally, ADCETRIS is being evaluated broadly in more than 20 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.

U.S. Important Safety Information

BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.

Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.

Warnings and Precautions:

• Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
• Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, interrupt the infusion. If anaphylaxis occurs, immediately and permanently discontinue the infusion.
• Hematologic toxicities: Grade 3 or 4 anemia, thrombocytopenia and prolonged (≥1 week) severe neutropenia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Closely monitor patients for fever. If Grade 3 or 4 neutropenia develops, manage by G-CSF support, dose delays, reductions or discontinuation.
• Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis/septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
• Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
• Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
• Stevens-Johnson syndrome (SJS): SJS has been reported with ADCETRIS. If SJS occurs, discontinue ADCETRIS and administer appropriate medical therapy.
• Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.

Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.

Drug Interactions:
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to MMAE.

Use in Specific Populations:
MMAE exposure is increased in patients with hepatic impairment and severe renal impairment.

For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.

Certain of the statements made in this press release are forward looking, such as those, among others, relating to our goal to establish ADCETRIS as the foundation of therapy for a broad array of CD30-positive malignancies. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks that data resulting from additional trials with ADCETRIS will not support approvals in any of the studied indications. In addition, as our other drug candidates or those of our collaborators advance in clinical trials, adverse events may occur which affect the future development of those drug candidates and possibly other compounds using similar technology. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended September 30, 2013 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.